The road is fully blocked while emergency services are at the scene, and motorists are advised to delay travel or take an alternate route.
A Hato Hone St John spokesperson said they are currently on scene with two ambulances and one helicopter.
More units are on the way to the scene.
St John said one person in a serious condition was transported to Dunedin Hospital by helicopter.
Another person in a serious condition and one in a moderate condition were transported to Lakes District Hospital by ambulance.
Two other people who received minor injuries were treated at the scene.